Initial Treatment of Tuberculosis Your name Institution/organization Meeting Date International Standards 7, 8, 10, 13, 17, 21.

Initial Treatment of Tuberculosis

Your name Institution/organizationMeetingDate

International Standards 7, 8, 10, 13, 17, 21

ISTC TB Training Modules 2009


Objectives: At the end of this presentation,participants will have an understanding of:

Drug regimens used in the initial treatment of both pulmonary and extrapulmonary tuberculosis

The basis for the public health benefits of treating tuberculosis

The clinical and microbiological effects of treatment The rationale for patient monitoring and reporting The main adverse effects of antituberculosis drugs



Overview: Effect of appropriate

treatment on public health First-line treatment

recommendations Treatment of extrapulmonary

tuberculosis Monitoring of treatment Adverse reactions Recording and reporting

International Standards 7, 8, 10, 13, 17, and 21


Standards for Treatment


Initial Treatment of TuberculosisStandards 7 & 8


Standard 7: Public Health Responsibility

Any practitioner treating a patient for tuberculosis is assuming an important public health responsibility to prevent ongoing transmission of the infection and the development of drug resistance. To fulfill this responsibility the practitioner must not only prescribe an appropriate regimen, but also utilize local public health services and other agencies, when necessary, to assess the adherence of the patient and to address poor adherence when it occurs.


Effect of Treatment on Public Health

Why is TB Treatment a Public Health Measure?

Effective treatment rapidly kills organisms, reducing the bacillary population in respiratory secretions, thus reducing the potential for transmission.

Effective multiple-drug treatment greatly reduces the risk of resistant organisms emerging.

Effective treatment decreases the duration and severity of illness and reduces the risk of death.


Effect of Treatment on Public Health

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120

140

160

180

200

220

1980 1985 1990 1995 2000

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DOTS 1990

PTB falling at 6%/yr

case finding

Effects of Treatment on the Incidence of Tuberculosis in Peru


Standard 8: Initiation of Treatment

All patients (including those with HIV infection) who have not been treated previously should receive an internationally accepted first-line treatment regimen using drugs of known bioavailability. The initial phase should consist of two months of isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), and ethambutol (EMB).

(1 of 2)


Mixed population (susceptible and resistant)

INH resistant bacilli

Emergence of INH resistant strain because of ineffective treatment (INH monotherapy)

Effective multi-drug therapy

Effect of Treatment on Bacillary Population

Weeks

Log

cfu

0 2 4 6 8 10 12 14 16 18 20 22 24


Months of Rx 0 5 7 9

INH

RIF

EMB

Smear + + + +

Culture + + + +

Susceptibility

INH R* R R R

RIF S* R R R

EMB S* S S R

* Results not known to clinician

Unintended Monotherapy and Resistance


Treatment Goals

Microbiological Goals of Antituberculosis Chemotherapy Kill tubercle bacilli rapidly

(early bactericidal effect) Prevent the emergence of drug

resistance Eliminate persistent bacilli to prevent

relapse (sterilizing effect)


Activities of Antituberculosis Drugs

Highest ++++ High +++ Intermediate ++ Low +

DrugEarly

bactericidal activity

Preventing drug

resistance

Sterilizing activity

Isoniazid ++++ +++ ++

Rifampicin ++ +++ ++++

Pyrazinamide + + +++

Streptomycin ++ ++ ++

Ethambutol ++ - +++ ++ +


Standard 8: Continuation of Treatment

The continuation phase should consist of isoniazid and rifampicin given for four months

The doses of antituberculosis drugs used should conform to international recommendations

Fixed-dose combinations (FDCs) of two (INH and RIF), three (INH, RIF, and PZA), and four (INH, RIF, PZA, and EMB) drugs are highly recommended

(2 of 2)


Treatment Recommendations

1. Associated with higher rate of acquired drug resistance and must be given using directly-observed therapy. Where feasible, daily dosing is preferred. May consider daily initiation phase, then 3x week continuation phase. 3x weekly dosing not recommended if living with HIV or living in an HIV-prevalent setting.

New Patients (not previously treated)

Initial Phase(2 months)

Continuation Phase(4 months)

INH, RIF, PZA, EMB daily INH, RIF daily

INH, RIF, PZA, EMB1 3x/wk. INH, RIF 3x/wk


Dose Recommendations

Drug Daily 3x Week

INH 5 (4-6), max 300/d 10 (8-12), max 900/d

RIF 10 (8-12), max 600/d 10 (8-12) max 600/ d

PZA 25 (20-30), max 2000/d 35 (30-40), max 3000/d

EMB 15 (15-20), max 1600/d 30 (25-35), max 2400/d

Streptomycin 15 (12-18) 15 (12-18)

Adults: mg/kg (range)


Standard 17: Treat Co-morbid Disease(1 of 2)

All providers should conduct a thorough assessment for co-morbid conditions that could affect tuberculosis treatment response or outcome

At the time the treatment plan is developed, the provider should identify additional services that would support an optimal outcome for each patient and incorporate these services into an individualized plan of care


This plan should include assessment of and referrals for treatment of other illnesses with particular attention to those known to affect treatment outcome, for instance care for diabetes mellitus, drug and alcohol treatment programs, tobacco smoking cessation programs, and other psychosocial support services, or to such services as antenatal or well baby care

Standard 17: Treat Co-morbid Disease(2 of 2)


Treatment of Extrapulmonary TB


In general, extrapulmonary tuberculosis is treated the same as pulmonary tuberculosis

Some experts recommend extending the duration of therapy in patients with:

• Meningeal tuberculosis

• Bone/joint tuberculosis

Corticosteroids may be useful adjunctive treatment in some forms of extrapulmonary tuberculosis



Treatment Duration and Use of Steroids

Site Length of Rx (mos.) Corticosteroids

Lymph node 6 No

Bone/Joint 6-9 No

Pleural 6 No

Pericarditis 6 Yes

CNS 9-12 Yes

Disseminated 6 No

Genitourinary 6 No

Abd/Peritoneal 6 No



Monitoring Treatment for TBand Public HealthReportingStandards 10, 13, & 21


Standard 10: Monitoring Treatment

1 of 2

Response to therapy in patients with pulmonary tuberculosis should be monitored by follow-up sputum smear microscopy (2 specimens) at the time of completion of the initial phase of treatment (2 months).

If the sputum smear is positive at completion of the initial phase, sputum smears should be examined again at 3 months and, if possible, culture and drug susceptibility testing should be performed.

(1 of 2)


Standard 10: Monitoring Treatment

2 of 2

In patients with extrapulmonary TB and in children, the response to treatment is best assessed clinically.

(2 of 2)


Isoniazid

Rifampicin

Pyrazinamide

Ethambutol

0 1 2 3 4 5 6Months

Initial Phase Continuation Phase

DiagnosticEnd of intensive phase

Assessment for failure

Completion

Monitoring: Timing of Sputum Specimens

[*Obtain if smear-positive at month 2]


Treatment Outcomes for Pulmonary TB

98%64%

32%

20%18%

50%

10%

Dead

Sputum negative

Sputum positive

No Chemotherapy

PoorChemotherapy

Good Chemotherapy

0.8%

1.2%

Grzybowski S et al, Bull Int Union Tuberc 1978; (53)2: 70-5


Monitoring: Adverse Reactions

• Drugs are listed in order of relative likelihood of causing adverse reaction.

• INH/RIF and RIF/PZA appear to have synergistic effects in causing hepatitis

Adverse Reaction

Drugs

Rash PZA, INH, RIF, EMB

Gastrointestinal intolerance

PZA, RIF

Liver toxicity

PZA, INH, RIF

Peripheral neuropathy

INH, (EMB)

Optic neuritis

EMB

Gout PZA


Adverse Reactions: Rash

Severe skin rash from thioacetazone

Classic drug-related rash


Drug-induced HepatotoxicityHepatotoxic reactions: Transaminase elevation age-dependent

with INH Transaminase elevation dose-dependent

with PZA Cholestasis (increase in bilirubin and

alkaline phosphatase) with RIF Symptoms imply significant hepatotoxicity (Mild transaminase elevation may not be

clinically significant)


Managing Hepatotoxicity

Management Hold all medications and follow liver

enzymes for significant hepatotoxicity Re-challenge depends on circumstances

and severity of liver dysfunction In general, patients should be restarted

with EMB (the least hepatotoxic drug) and RIF, usually followed in several days by INH if there is no worsening of liver function


A written record of all medications given, bacteriologic response, and adverse reactions should be maintained for all patients

Standard 13: Monitoring Record


Standard 21: Reporting Cases

All providers must report both new and retreatment tuberculosis cases and their treatment outcomes to local public health authorities, in conformance with applicable legal requirements and policies.

ISTC Training Modules 2008


Summary: Appropriate treatment and assessment of

adherence to treatment is an important public health issue.

The use of internationally accepted first-line treatment regimens is associated with a high cure rate and a low risk of acquired drug resistance.



Summary (cont.): Pulmonary and extrapulmonary TB are

generally treated with the same regimens. (Exception: extended duration in meningeal and bone/joint disease.)

Treatment includes assessment and services for co-morbid conditions that may effect tuberculosis treatment outcomes

Monitoring for both response to treatment and for potential adverse events is essential.



Summary: ISTC Standards Covered*

Standard 7: Practitioners assume an important public health responsibility in ensuring both appropriate treatment regimens and assessment of treatment adherence for their patients.

* Abbreviated versions



Standard 8: All patients (including those with HIV infection) who have not been previously treated should receive an internationally accepted treatment regimen of known bioavailability:• Initial phase: 2 months INH, RIF, PZA, and

EMB• Continuation phase: 4 months INH and RIF

The doses of anti-TB drugs used should conform to international recommendations. Fixed-dose combinations are highly recommended.



Standard 10: Response to therapy in patients with pulmonary TB should be monitored by follow-up 2 sputum smears at the end of the initial phase, and if positive, repeated at the end of 3 months (if positive at 3 months, obtain culture and DST). In extrapulmonary TB and in children, the response to treatment is best assessed clinically.




Standard 13: A written record of all medications given, bacteriologic responses, and adverse reactions should be maintained for all patients.

Standard 17: All providers should conduct a thorough assessment and provide services or referrals for co-morbid conditions with particular attention to those known to effect treatment outcome




Standard 21:

All providers must report both new and retreatment TB cases and their treatment outcomes to local public health authorities




Alternate Slides


Purpose of ISTC


ISTC: Key Points

21 Standards (revised/renumbered in 2009) Differ from existing guidelines: standards

present what should be done, whereas, guidelines describe how the action is to be accomplished

Evidence-based, living document Developed in tandem with Patients’ Charter

for Tuberculosis Care Handbook for using the International

Standards for Tuberculosis Care


Audience: all health care practitioners, public and private

Scope: diagnosis, treatment, and public health responsibilities; intended to complement local and national guidelines

Rationale: sound tuberculosis control requires the effective engagement of all providers in providing high quality care and in collaborating with TB control programs

ISTC: Key Points


Questions



1. A 28 year-old woman taking standard four-drug treatment for TB for five weeks now complains of nausea, vomiting, and right upper-quadrant discomfort. When seen in clinic she is noted to have scleral icterus and right upper-quadrant tenderness. Her urine is dark colored. What is the appropriate action to take at this time?

A. Stop all drugs

B. Stop isoniazid

C. Give pyridoxine (vitamin B6)

D. Replace pyrazinamide with streptomycin



2. A 68 year-old woman with smear-positive TB needs to start treatment. She lives too far to be given directly-observed treatment (DOT) by your office. Which treatment regimen is preferred for this patient?

A. Isoniazid and ethambutol for twelve months

B. Isoniazid/rifampicin/ethambutol for the first two months, followed by isoniazid/rifampicin for an additional four months

C. Fixed-dose combination of isoniazid/rifampicin/pyrazinamide for nine months

D. Fixed-dose combinations of isoniazid/rifampicin/ethambutol/pyrazinamide for the first two months, followed by isoniazid/rifampicin for an additional four months


Initial Treatment of Tuberculosis3. In considering treatment for extrapulmonary

disease, all of the following statements are correct except:

A. Extrapulmonary disease is a sign of disseminated disease, and therefore always requires a longer duration of treatment

B. Most presentations of extrapulmonary TB can be treated with the same standard six month regimens used for pulmonary TB

C. Extending the duration of therapy is recommended by many experts for central nervous system (CNS) and bone/joint extrapulmonary TB

D. Corticosteroids are sometimes recommended for pericardial and central nervous system (CNS) extrapulmonary TB

Initial Treatment of Tuberculosis Your name Institution/organization Meeting Date International Standards 7, 8, 10, 13, 17, 21.

Documents

tb treatment

treatment slide

istc tb training modules

continuation of treatment

initiation of treatment

resistance slide

line treatment regimen

peru slide